Calmodulin-like protein increases filopodia-dependent cell motility via up-regulation of myosin-10

J Biol Chem. 2007 Feb 2;282(5):3205-12. doi: 10.1074/jbc.M607174200. Epub 2006 Nov 26.


Human calmodulin-like protein (CLP) is an epithelial-specific protein that is expressed during cell differentiation but down-regulated in primary cancers and transformed cell lines. Using stably transfected and inducible HeLa cell lines, we found that CLP expression did not alter the proliferation rate and colony-forming potential of these cells. However, remarkable phenotypic changes were observed in CLP-expressing compared with control cells. Soft agar colonies of CLP-expressing cells had rough boundaries, with peripheral cells migrating away from the colony. Cells expressing CLP displayed a striking increase in the number and length of myosin-10-positive filopodia and showed increased mobility in a wound healing assay. This increase in wound healing capacity was prevented by small interference RNA-mediated down-regulation of myosin-10. Fluorescence microscopy and Western blotting revealed that CLP expression results in up-regulation of its target protein, myosin-10. This up-regulation occurs at the protein level by stabilization of myosin-10. Thus, CLP functions by increasing the stability of myosin-10, leading to enhanced myosin-10 function and a subsequent increase in filopodial dynamics and cell migration. In stratified epithelia, CLP may be required during terminal differentiation to increase myosin-10 function as cells migrate toward the upper layers and establish new adhesive contacts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Calmodulin / genetics
  • Calmodulin / physiology*
  • Cell Division
  • Cell Movement / physiology*
  • DNA Primers
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Myosins / genetics
  • Myosins / metabolism*
  • Peptide Fragments / chemistry
  • Pseudopodia / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • CALML3 protein, human
  • Calmodulin
  • DNA Primers
  • MYO10 protein, human
  • Peptide Fragments
  • Myosins